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[Risk factors for the degeneration of the choroid naevi: a retrospective study of 135 cases].

INTRODUCTION: We have carried out a retrospective study of 135 patients followed at Curie Institute for choroidal naevus between March 1983 and June 1997. PATIENTS AND METHODS: 54 patients presented naevi considered as benign and 81 patients presented suspicious choroidal naevi (with at least one of the following findings: visual symptoms; serious detachment of the retina; orange pigment; thickness greater than 2mm or a diameter greater than 7mm). These suspicious naevi were followed more carefully. The median follow-up was 49 months. The median diameter of the lesions was 6mm and the median thickness was 1.5mm. We studied the age of the patients, clinical symptoms, the presence or absence of orange pigment, drusen and serious detachment, and the angiographic and echographic findings. RESULTS: 3 patients died of unrelated cause; 7 patients were lost to follow-up; 30 patients presented documented growth; 4 of them belonged to the group considered as benign and 26 to the group considered as suspicious, with a significant difference between the groups. The lesions that grew were treated by proton beam or I125 patches. The risk factors for growth that were statistically significant were the presence of visual symptoms, pin points, orange pigment, serous detachment and thickness greater than 2mm. With drusen, the risk for growth was significantly less. DISCUSSION: These results are very similar to those published in the literature concerning risk factors for growth of choroidal nevi. The absence of metastatic spread in patients whose nevi have grown show that it is possible to monitor choroidal naevi if there is a doubt as to the malignant or benign nature of the lesion. CONCLUSION: It is important to determine if a choroidal naevus is suspicious or benign and to propose closer follow-up for suspicious lesions.

Adult↗

Quantifying changes in RPE and choroidal vasculature in eyes with age-related macular degeneration.

PURPOSE: An image-analysis technique was developed to quantify changes in the retinal pigment epithelium (RPE) and choriocapillaris in eyes of deceased donors with age-related macular degeneration (AMD). METHODS: Both eyes of two donors with AMD and of one normal control donor were used to develop this technique. After removal of the anterior segments, the eyecups were hemisected through the macula, with the disc included in one half of the eyecup. The choroid with RPE cells was dissected from the sclera and incubated for alkaline phosphatase (APase) activity, and the pigment was partially bleached with H2O2. The APase-incubated choroid was flat embedded and sectioned after image and morphometric analyses. Quantitative computer-assisted morphometric analyses of the two AMD-affected eyes (cases 1 and 2) were compared with analysis of the normal eye of a 70-year-old control subject (case 3). RESULTS: The right eye in case 1 had geographic atrophy (GA) and demonstrated a large area in the posterior pole with very few RPE cells (90% loss of RPE), but the border of the area of RPE atrophy was not well defined. The density of choroidal blood vessels in this area was reduced 30% to 50%, compared with the same regions in the control eye. No area was completely devoid of choriocapillaris. Clinically undetected choroidal neovascularization (CNV) was observed in the right eye in case 1 in both the periphery and the macula and was generally associated with surviving RPE cells. The right eye in case 2 had GA (areolar RPE atrophy) and demonstrated a reduction in vascular density in the area from disc to macula that was even greater than that in the eye in case 1 (53% reduction in the submacular region). RPE atrophy between the disc and macula was almost complete. The border of the RPE defect was clearly delineated and coincided closely with the area of decreased choroidal vascular density. Surviving choriocapillaris in the area of RPE atrophy was significantly narrower than choriocapillaris in the control subject and in normal areas of the eyes with GA (P < 0.0001). CONCLUSIONS: In these eyes with GA, RPE atrophy was more severe than loss of choriocapillaris. Surviving choriocapillaris in areas with complete RPE loss was highly constricted. The association of surviving RPE cells with CNV suggests that RPE cells may furnish a stimulus for new vessel formation or stabilization.

Aged↗

[Expression of vascular endothelial growth factor and its receptor in experimental choroidal neovascularization in rat].

OBJECTIVE: To study the expressions of vascular endothelial growth factor and its receptor FLK1 in krypton laser-induced choroidal neovascularization (CNV) in Brown Norway rat. METHODS: Thirty anesthetized male Brown Norway rats received krypton laser (647 nm, 360 mW, 50 micro m, 0.05 s) to induce CNV. Fundus fluorescein angiography examinations were performed just before euthanasia on days 3, 7, 14, 21, 28 and 56 after laser photocoagulation. The retina was processed for histopathology analysis. VEGF mRNA, VEGF and FLK1 expressions were demonstrated using in situ hybridization and immunohistochemistry staining respectively. RESULTS: VEGF mRNA expression was mainly observed in the vascular endothelial cells, the ganglion cells, the inner nuclear layers, the retinal pigment epithelial cells in normal retina and the vascular endothelial cells of normal choroid of BN rat. VEGF mRNA expressed in the vascular endothelial cells, the ganglion cells, the inner nuclear layers, lesion of outer nuclear layers in retina on days 3 after photocoagulation, but CNV wasn't detected. The level of VEGF mRNA expression in retina was decreased after 3 days (P < 0.01). CNV was firstly observed on day 7 after photocoagulation by FFA and histopathology. The area and density of positively stained cells for VEGF mRNA in CNV were increased during the development of CNV (P < 0.01) and no significant change after days 21 (P > 0.05). FLK1 was detected in the vascular endothelial cells, the ganglion cells of normal retina and the vascular endothelial cells of choroid. The staining of FLK1 was positive in laser induced CNV after days 7, the level of the receptor expression was increased during the development of CNV (P < 0.01) and was not significantly changed after days 21 (P > 0.05). CONCLUSIONS: VEGF and its receptor FLK1 accumulation and combination in the lesion of retina and choroid are related to choroidal neovascularization induced by laser.

Animals↗

The abnormal choroidal vessels in aged patients.

BACKGROUND: To show the abnormal choroidal vessels in aged patients with indocyanine-green angiography (ICGA). METHODS: ICGA was performed in 350 patients with TOPCON TRC-50IA fundus camera. The images were recorded and retrospectively reviewed. RESULTS: Five aged patients out of 350 cases were found to have abnormal choroidal vessels. The incidence was 1.43%. The abnormal choroidal vessels showed round- shapet, focal enlargement, abnormal shape and entrance, satellite appearance, and vascular loops. These might be due to congenital abnormality of choroid. CONCLUSION: ICGA could be used to observe the abnormal choroidal vessels.

Aged↗

Functional loss in age-related Bruch's membrane change with choroidal perfusion defect.

During a prospective study of age-related macular degeneration, evidence of diffuse Bruch's membrane disease was sought using fluorescein angiographic evidence of a prolonged choroidal filling phase. Dark-adapted static perimetry was done on eight eyes with this angiographic sign and on six eyes with a similar number of drusen but no manifest choroidal perfusion abnormality. Scotopic threshold was measured using the Humphrey automated perimeter and fine matrix mapping. In eyes without delayed choroidal perfusion, no discrete areas of increased threshold were found compared with the background sensitivity. By contrast, in seven of the eight eyes with fluorescein angiographic evidence of prolonged choroidal filling, discrete areas of scotopic threshold elevation (up to 3.4 log units) were recorded; these corresponded closely to regions of choroidal perfusion abnormality. It was postulated that diffuse deposits of abnormal material might account for both the perfusion abnormality and functional loss by acting as a diffusion barrier between the choriocapillaris and the retinal pigment epithelium.

Aged↗

Comparative histopathological study of free-running mode and continuous wave Nd:YAG laser photocoagulation of monkey retina and choroid.

The effects of free-running mode (FRM) or continuous wave (CW) Nd:YAG laser application on the retina and choroid of 12 monkeys were examined periodically up to 24 months by light and electron microscopes. FRM Nd:YAG laser produced severe choroidal hemorrhage even in mild burns, because of the extensive coagulation of melanocytes at the center of the burned lesion. The rupture of Bruch's membrane did not depend on the power of the laser. On the other hand, CW Nd:YAG laser rarely produced subretinal hemorrhage through the rupture of Bruch's membrane in the medium-grade and severe burns. However, choroidal hemorrhage was seen histologically even in mild CW burned lesions. In the healing stage of mild FRM burned lesions the retinal pigment epithelium (RPE) and choroidal fibroblasts showed different repair processes. FRM medium-grade burned lesions showed the proliferation of Müller cells, while CW burns showed the regeneration and proliferation of RPE, Müller cells and fibroblasts. Because of the difference in the repair processes evoked by these two modes of laser application, these findings suggest that CW Nd:YAG laser is preferable for the treatment of subretinal and choroidal disorders.

Animals↗

[Choroidal detachment associated with spontaneous carotid cavernous fistula].

A rare case is presented in which an 87-year-old woman with choroidal detachment was subsequently found to have an atypical carotid cavernous fistula (CCF). In this case, the intraocular pressure of the affected eye was higher than that of the contralateral eye. However, tonography showed no increased ocular pulse (amplitude of Schioetz reading) of the affected eye, which is characteristic of CCF. Choroidal detachment accompanied with CCF is thought to be a result of severe choroidal hemostasis and transudation caused by increased episcleral venous pressure. Furthermore, the enlarged perichoroidal space due to choroidal detachment reduced the ocular pulse of the affected eye. This combination may not be as rare as it has been previously reported. Attention to these symptoms can provide clues to the elucidation of the pathogenesis of choroidal detachment.

Aged↗

[Studies on ocular blood circulation--effects of oxygen on choroidal circulatory disorders].

Experimental choroidal circulatory disorder was induced by diathermy coagulation in albino rabbit to investigate the effect of oxygen on choroidal blood flow in the area. Choroidal blood flow was measured by a hydrogen clearance method using electrolysis before and after the oxygen inhalation. Oxygen was inhaled for 30 minutes at 1 atmosphere using an open mask method in order to stabilize the arterial blood CO2 concentration. After inhalation of oxygen, normal choroidal blood flow showed a 24.9% decrease from control value, but no significant difference was seen in experimental choroidal circulatory disorder. These results suggested that the inner tissue metabolic CO2 inhibited the effect of vascular constriction in hyperoxemia.

Administration, Inhalation↗

Choroidal melanomas and paving stone degeneration.

The association between malignant melanoma of the choroid and paving stone degeneration noted anterior to this tumor is described in five eyes. Presumably, the paving stone lesions develop from peripheral choroidal insufficiency induced by vascular compromise from the space-occupying tumor. This phenomenon is not unique to choroidal melanomas, for we have also observed it in association with a choroidal nevus and a metastatic carcinoma to the choroid.

Adult↗

Immunohistochemical localization of the glucose transporter GLUT1 in choroid plexus papillomas.

Normal chroid plexus tissue and five choroid plexus papillomas were examined with antibody specific for the glucose transporter GLUT1, one isoform of facilitated-diffusion glucose transporters, using the avidin-biotin-peroxidase complex (ABC) technique. GLUT1 in normal choroid plexus was localized at the basolateral plasma membrane of almost all epithelial cells. In three of five tumors, GLUT1 immunoreactivity was observed. A positive reaction was demonstrated at the plasma membrane of tumor cells. The number of GLUT1-positive cells was, however, much smaller than that of the normal choroid plexus. Our results suggest that GLUT1 expression in the choroid plexus is restrained during the course of transformation and that choroid plexus papilloma is composed of various differentiation tumor cells.

Adolescent↗

[Results of perifoveal argon laser coagulation of subfoveal choroid neovascularization in age related macular degeneration].

BACKGROUND: The treatment of patients with subfoveal choroidal neovascular membrane in age-related macular degeneration is unsatisfactory because only a limited number of patients are eligible. The aim of this study was to prospectively evaluate a new perifoveal treatment technique in patients with subfoveal choroidal neovascular membrane. METHODS: Between April 1992 and January 1994, 385 patients underwent clinical examination and fluorescein angiography. Eligibility criteria were met by 21 (5.5%) patients (22 eyes): well or poorly defined subfoveal choroidal neovascular membrane (< or = 3.5 disc diameters), without fibrosis, with visual acuity < or = 0.25. Visual acuity, morphological findings and complications were studied. The follow-up period was 12-32 months. RESULTS: The visual acuity before laser treatment ranged from counting fingers up to 0.25 (median 0.06). At the end of the follow-up (median 18 months) 28% (6/21) of patients showed a better visual acuity, whereas 44% (9/21) were unchanged and 28% (6/21) had deteriorated compared to visual acuity before treatment. In 71% (15/21) of eyes, resolution of the choroidal neovascular membrane was achieved with development of an atrophic laser scar. CONCLUSION: The visual outcome and the morphological findings after perifoveal laser treatment of subfoveal choroidal neovascular membrane in age-related macular degeneration show it to be an alternative method of treatment with favourable results. Due to inclusion criteria it is suitable only for a limited number of patients.

Aged↗

[Disorders of choroidal circulation in diabetic maculopathy].

Diabetic maculopathy is classified into 3 types, namely, macular edema, ischemic maculopathy, and pigment epitheliopathy. Blood-retinal barrier disturbance and the influence of the posterior vitreous membrane have been reported as the cause of diabetic maculopathy. However, its association with the choroidal circulation feeding the outer layer of the retina which involves the outer blood-retinal barrier has not been clarified yet. In this work, we studied the presence of the choroidal circulatory disturbance by performing indocyanine green angiography (IA) on patients with diabetic maculopathy. Choroidal circulatory disturbance was also differentiated from fluorescent block with a scanning laser ophthalmoscope (SLO). The proportion of hypofluorescence observed in IA was 4 eyes in 2 patients among 37 eyes in 24 patients (11%) in the macular edema group, 3 eyes in 2 patients among 14 eyes in 10 patients (21%) in the ischemic maculopathy group, and 26 eyes in 17 patients among 33 eyes in 22 patients (79%) in the pigment epitheliopathy group. Of the cases showing hypofluorescence in IA in the pigment epitheliopathy group, 4 eyes in 4 patients had hypofluorescence due to both choroidal circulatory disturbance and fluorescent block. This suggests that the choroidal circulation disturbance is partly involved in diabetic maculopathy mainly in the pigment epitheliopathy group.

Adult↗

Suppression of laser-induced choroidal neovascularization by oral tranilast in the rat.

PURPOSE: To determine whether tranilast administered to pigmented rats inhibits formation of choroidal neovascularization induced by diode-laser photocoagulation. METHODS: Female Brown Norway rats were used. On day 0, choroidal neovascularization was induced by diode-laser photocoagulation, using a setting of 75 microm spot size, 0.1 second's duration, and 100 mW intensity. Tranilast (200 or 600 mg/kg per day) was administered orally twice daily for 14 days. Indomethacin (1 and 5 mg/kg per day) was administered orally once a day for 14 days. Choroidal neovascularization was evaluated on days 7 and 14 by fundus photography and fluorescein angiography. Late-phase fluorescein angiography was scored according to four grades. The animals were killed on day 14, and the lesions were evaluated histologically. RESULTS: In the vehicle-treated group, 34 of 35 burns (97%) showed fluorescein staining and late leakage on day 14. Choroidal neovascularization was identified by light microscopy in all the lesions that showed fluorescein staining and late leakage. The score of fluorescein staining was reduced in rats given 200 mg/kg per day or 600 mg/kg per day (P < 0.01) of tranilast. The thickness of the laser-induced lesions was reduced in a dose-dependent manner by tranilast, a significant difference was observed with 600 mg/kg per day (P < 0.05). Oral indomethacin treatment did not reduce fluorescein staining on day 14. CONCLUSIONS: Tranilast inhibits the development of choroidal neovascularization in this experimental model.

Administration, Oral↗

[Idiopathic polypoidal choroidal vasculopathy: its extreme aspects in one patient--case report].

To describe a case of idiopathic polypoidal choroidal vasculopathy and the role of indocyanine green angiography findings in the differential diagnosis of exudative maculopathies, particularly with age-related macular degeneration, and the extreme evolution of idiopathic polypoidal choroidal vasculopathy in one patient. A patient with vitreous hemorrhage was examined and evaluated by fluorescein and indocyanine green angiographies in the right eye and with hemorrhagic detachment of the retinal pigment epithelium in the left eye. The patient was treated by pars plana vitrectomy in the right eye which was followed by retinal detachment and vision loss. In the left eye an involution of the hemorrhagic detachment of the retinal pigment epithelium with preservation of the vision was seen. The idiopathic polypoidal choroidal vasculopathy seems to be a distinct clinical entity that can and should be differentiated from age-related macular degeneration and the fluorescein and indocyanine green angiographies should be performed to evaluate the choroidal vasculature in an attempt to establish a more definitive diagnosis. Particularly in this case the entity had an extreme clinical course in the patient.

Choroid↗

Choroidal laser Doppler flowmetry in healthy subjects.

OBJECTIVE: To evaluate normal choroidal blood flow and its relationship with various factors such as age, systemic blood pressure, and intraocular pressure (IOP). METHODS: A total of 70 healthy subjects were recruited. Choroidal blood flow was assessed using a method based on laser Doppler flowmetry (LDF) technique. The LDF parameters of velocity, volume, and flux were obtained. The influence of age, mean systemic blood pressure, IOP, smoking, and sex on choroidal hemodynamic parameters was assessed in a multiple linear regression model. The correlations between interocular difference in IOP and interocular differences in the LDF parameters were assessed by means of the Pearson linear correlation factor. RESULTS: Velocity decreased significantly (P = .03) with advancing age of the subjects and volume increased significantly (P = .02) with increasing IOP. Mean blood pressure, smoking, and sex had no influence on the choroidal LDF parameters. Interocular difference in IOP correlated significantly with interocular difference in volume (R = 0.34, P<.005). CONCLUSION: Choroidal blood flow velocity decreased with increasing age of the subjects, while the volume of moving erythrocytes decreased with lower IOP.

Adolescent↗

Combination of clinical factors predictive of growth of small choroidal melanocytic tumors.

OBJECTIVE: To better define the effect of individual risk factors and combinations thereof on the growth of small choroidal melanocytic tumors. DESIGN: Retrospective analysis. SETTING: Clinical practice of ocular oncology. PATIENTS: The study included 1287 patients with small suspicious choroidal melanocytic tumors, measuring 3 mm or less in thickness, managed with observation. RESULTS: On multivariate analysis, the clinical risk factors predictive of growth of small choroidal melanocytic tumors include tumor thickness greater than 2.0 mm, posterior tumor margin touching the disc, visual symptoms, orange pigment, and subretinal fluid. Tumor growth was detected in 4% of those patients with no risk factors. Growth was detected in approximately 36% of patients with 1 risk factor, 45% of patients with 2 risk factors, 50% of patients with 3 risk factors, 51% of patients with 4 risk factors, and 56% of patients with all 5 risk factors. The combination of risk factors offering the greatest risk for growth was tumor thickness greater than 2.0 mm, tumor margin touching disc, and subretinal fluid that was associated with tumor growth in 63% of the affected patients. The relative risk for growth was 1.9 for 1 factor, 3.8 for 2 factors, 7.4 for 3 factors, 14.1 for 4 factors, and 27.1 for all 5 risk factors combined. CONCLUSIONS: Five risk factors for growth of small choroidal melanocytic tumors have been identified. The combinations of various factors increase the risk for tumor growth from 4% if no factors are present to more than 50% if 3 or more risk factors are present. These factors may be important when counseling patients with small suspicious choroidal melanocytic tumors.

Choroid Neoplasms↗

The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma, II: characteristics of patients enrolled and not enrolled. COMS Report No. 17.

OBJECTIVES: To describe characteristics of patients evaluated for the Collaborative Ocular Melanoma Study (COMS) randomized clinical trial of iodine 125 brachytherapy for choroidal melanoma by enrollment status, and to compare characteristics of patients enrolled with those of patients with tumors of eligible size who did not enroll in order to assess the extent to which findings from the clinical trial can be generalized to future patients. METHODS: For all patients diagnosed with choroidal melanoma and evaluated for the clinical trial at COMS centers from November 1986 through July 31, 1998, selected data were transmitted to the COMS Coordinating Center, Baltimore, Md, where they were integrated and analyzed. Data included ophthalmic and medical history, examination findings, and visual acuity measurements recorded prior to enrollment; standardized A- and B-scan echographic examination findings; and wide-angle fundus photographs and fluorescein angiograms. RESULTS: Of 8712 patients with choroidal melanoma, 5046 had tumors of eligible size; of these, 2882 (57%) were eligible for enrollment, and 1317 (46% of eligible patients, 26% of patients with tumors of eligible size) enrolled. Most differences between eligible and ineligible patients corresponded to eligibility and exclusion criteria. However, ineligible patients were older and had thicker tumors than eligible patients. Eligible patients who enrolled were slightly older and had larger tumors than those who did not enroll. Nearly half (48%) of enrolled patients had choroidal melanoma with the apex located temporal to the fovea, compared with 40% of eligible patients not enrolled and 29% of ineligible patients. CONCLUSIONS: This trial was designed to yield internally valid treatment comparisons through random assignment to treatment at time of enrollment. Information from this and other studies document that enrolled patients were similar to other patients with choroidal melanoma who were treated with 125I brachytherapy. These findings support the external validity of the trial and applicability of treatment findings to all patients who meet the criteria used to judge eligibility for the trial.

Adult↗

Three-dimensional ultrasound for the measurement of choroidal melanomas.

OBJECTIVE: To evaluate the reliability of 3-dimensional ultrasound (3D-US) for the measurement of choroidal melanomas. DESIGN: Retrospective case series. PARTICIPANTS: Forty-two consecutive cases of choroidal melanoma imaged with 3D-US. METHODS: Tumor measurements obtained with ophthalmoscopy, transillumination, standard ultrasound techniques, 3D-US, and pathological studies. Tumor diameters, heights, and volumes were compared. Our 3D-US tumor measurement techniques were tested for intraobserver and interscan reproducibility. RESULTS: Fifty 3D-US images were studied. The 3D-US tumor measurements were found to be reproducible (height coefficient of variation [CV] < or = 3%; diameter CV < or = 9.7%; volume CV < or = 13.2%). There was significant correlation with the usual methods of tumor measurement (diameter r = 0.76; height r > or = 0.98). Significant differences were found between measurements at pathological examination, as compared with both 2-dimensional and 3D-US height measurements (range, 0.73-0.83 mm). This finding was thought to be due to specimen shrinkage. Three-dimensional ultrasound was found to be at least as reproducible as clinical examination and standard ultrasound techniques used for measurement of diameter and height of choroidal melanomas. It was our impression that the 3D-US volume measurements accounted for the geometry of the tumor better than volume estimates calculated from basal area and tumor height. CONCLUSIONS: Three-dimensional ultrasound measurements of choroidal melanoma were reproducible, correlated well with other tumor measurement techniques, and can be used for measurement of choroidal melanomas.

Choroid Neoplasms↗